UPLC-MS/MS法同时测定患儿血浆中乙胺丁醇及异烟肼的浓度
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篇名: UPLC-MS/MS法同时测定患儿血浆中乙胺丁醇及异烟肼的浓度
TITLE:
摘要: 目的:建立同时测定患儿血浆中乙胺丁醇(EMB)及异烟肼(INH)浓度的方法。方法:血浆样品经乙腈沉淀蛋白后,采用超高效液相色谱-串联质谱法(UPLC-MS/MS)测定。以拉米夫定为内标,色谱柱为Waters ACQUITY® UPLC HSS T3,流动相为乙腈-水(含0.05%甲酸及15 mmol/L甲酸铵),梯度洗脱,流速为0.2 ml/min。采用电喷雾离子源,多反应监测方式进行正离子扫描,用于定量分析的离子对分别为m/z 205.2→116.0(EMB)、m/z 138.1→121.1(INH)、m/z 230.2→111.9(内标)。结果:EMB、INH血药浓度分别在10~5 000、50~5 000 ng/ml范围内线性关系良好,定量下限分别为10、50 ng/ml;日内、日间RSD<15%,相对回收率为98.7%~105.5%。临床检测4例肺结核患儿体内EMB、INH的血药浓度为94.5~99.7、55.1~80.9 ng/ml。结论:该方法分析快速、灵敏度高,适用于患儿EMB、INH血药浓度的监测及药动学研究。
ABSTRACT: OBJECTIVE: To establish a method for the simultaneous determination of ethambutol (EMB) and isoniazid (INH) in children’s plasma. METHODS: After precipitated with acetonitrile, plasma samples were determined by UPLC-MS/MS method. Using lamivudine as internal standard, Waters ACQUITY® UPLC HSS T3 column was adopted with mobile phase consisted of acetonitrile-water (containing 0.05% formic acid and 15 mmol/L ammonium formate) in gradient mode at the flow rate of 0.2 ml/min. By ESI, positive ion detection was conducted in MRM mode. The monitoring transition ion-pair was m/z 205.2→116.0 for EMB, m/z 138.1→121.1 for INH and m/z 230.2→111.9 for internal standard. RESULTS: The linear range of EMB and INH was 10-5 000 ng/ml and 50-5 000 ng/ml, respectively; the limits of quantitation were 10 and 50 ng/ml; RSDs of inter-day and intra-day were all lower than 15% and relative recoveries were 98.7%-105.5%. Plasma concentrations of EMB and INH in 4 children with tuberculosis were 94.5-99.7 and 55.1-80.9 ng/ml. CONCLUSIONS: The method is rapid and sensitive, which suitable for children’s plasma concentration monitoring of EMB and INH and pharmacokinetic study.
期刊: 2016年第27卷第20期
作者: 安静,董占军,张笑丹,刘洪涛
AUTHORS: AN Jing,DONG Zhanjun,ZHANG Xiaodan,LIU Hongtao
关键字: 乙胺丁醇;异烟肼;超高效液相色谱-串联质谱法;血药浓度;肺结核;患儿
KEYWORDS: Ethambutol; Isoniazid; UPLC-MS/MS; Plasma concentration; Pulmonary tuberculosis; Children
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